P832: PROSPECTIVE REAL-WORLD EVALUATION OF THE PREVALENCE OF T(11;14) IN MULTIPLE MYELOMA: THIRD INTERIM ANALYSIS FROM THE MEDICI STUDY
Authors: Maria Gavriatopoulou, Andrew Spencer, Daniel Coriu, Fernando Escalante Barrigón, Roman Hájek, Fernanda Seguro, Norma C. Gutiérrez, Sandra Basic Kinda, Massimo Offidani, Dorotea Beatriz Eugenia Fantl, Rosane Bittencourt, Anna Lysén, Vladimir Maisnar, Elham Askari, Joaquín Martinez-Lopez, Olivia Hughes, Rebekah Taylor, Kristin Lehn, Roby Joehanes, Jeremy Ross, Carlos Hader
Journal: HemaSphere (2023)

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Multiple myeloma (MM) is characterized by bone marrow (BM) infiltration of monoclonal plasma cells (PCs) harboring well-defined genetic aberrations, such as t(11;14). Venetoclax, a highly selective, potent oral BCL-2 inhibitor, has previously shown efficacy in patients (pts) with t(11;14) relapsed/refractory MM (RRMM) and is under investigation as targeted therapy in combination with dexamethasone for t(11;14) RRMM in the randomized phase 3 CANOVA study. Previous studies suggest 15–20% of pts with MM carry t(11;14). However, historical studies may underestimate t(11;14) prevalence as CD138 enrichment of PCs (plasma cell enrichment [PCE]) before fluorescence in situ hybridization (FISH) testing has not been, and currently is not, standard practice globally, despite enhanced t(11;14) detection with this method. MEDICI is an ongoing, global, prospective study evaluating t(11;14) prevalence using interphase FISH with PCE in newly diagnosed MM (NDMM) and RRMM. Aims: To report real-world t(11;14) prevalence based on MEDICI third interim analysis. Methods: The multicenter, non-interventional MEDICI study (NCT04721002) enrolled pts (≥18 years) who provided signed informed consent. BM aspirates were collected at diagnosis and/or disease relapse. Immunomagnetic particles (STEMCELL Technologies) were used to select CD138+ cells, thereby enriching PCs from BM aspirates. Vysis IntelliFISH CCND1/IGH XT FISH probe kit (Abbott) was used to evaluate t(11;14) status by FISH with PCE. The primary objective is to evaluate t(11;14) prevalence in NDMM and RRMM using interphase FISH with PCE, excluding patients who had a failed test. The primary endpoint is t(11;14) status of the earliest BM sample collected at initial diagnosis or across subsequent lines of therapies. Results: At the 16 January 2023 cutoff, 312 pts (NDMM, n=204; RRMM, n=108) were enrolled in 20 countries. Median age was 66 years, and most pts were male (53.5% vs 46.5% female) and Caucasian/White (83.3% vs 10.3% Hispanic/Latino, 2.9% Asian, 1.0% Black/African American, 2.6% unknown). ECOG performance status was ≤2 in 82.7% of pts, >2 in 4.5%, and unknown in 12.8%. Disease was ISS stage I in 30.8% of pts, stage II in 25.6%, stage III in 27.6%, and unknown in 16.0%. FISH testing was evaluable in 295 pts (94.6%), only 6 (2.0%) of whom had an indeterminate result. The observed overall t(11;14) prevalence (95% CI) was 20.7% (16.2–25.8). Prevalence of t(11;14) was 18.7% (13.5–24.8) in pts with NDMM and 24.7% (16.5–34.5) in pts with RRMM. The distribution of t(11;14)-positive pts across lines of therapy was 18.7% (13.5–24.8) in 1L, 20.6% (8.7–37.9) in 2L, and 27.3% (17.0–39.6) in 3L+. The distribution of t(11;14)-positive pts across disease stage was 20.7% (12.9–30.4) in stage I, 19.5% (11.3–30.1) in stage II, and 17.5% (9.9–27.6) in stage III. t(11;14) FISH fusion patterns were consistent between NDMM (1F, 29.7%; 2F, 45.9%; ≥3F, 16.2%) and RRMM (1F, 33.3%; 2F, 45.8%; ≥3F, 16.7%). Available del(17p) testing (evaluable pts: NDMM, 128/204; RRMM, 52/108) showed the highest rate of del(17p) occurred in pts with t(11;14)-positive NDMM (18.9% [7/37]) compared with t(11;14)-negative NDMM (8.8% [14/159]; Table). Available gain(1q) testing (evaluable pts: NDMM, 124/204; RRMM, 38/108) showed the highest rate of gain(1q) occurred in pts with t(11;14) RRMM (29.2% [7/24]) compared with t(11;14)-negative RRMM (10.1% [7/69]). Summary/Conclusion: MEDICI third interim analysis showed an overall t(11;14) prevalence of 20.7% as detected by FISH with PCE. Rates of poor prognostic markers del(17p) and gain(1q) were highest in t(11;14) NDMM and t(11;14) RRMM, respectively.Keywords: Plasma cells, Myeloma, “t(11;14)”